The overall objective of this proposal is the application of physico-chemical rationale and techniques to the study of physiological and pathological processes. Certain biological fluids (bile, intestinal content, plasma and lymph) contain lipids solubilized in aqueous systems. Other lipids, particularly those of the membranes of cells (including myelin) and the membranes of intracellular organelles such as microsomes and mitochondria contain lipids which are not soluble but are structured in such a way as to combine fluidity with stability. Finally, certain lipids, occurring for instance in adipose tissues, adrenal glands, gonads or in the fatty streak of early atherosclerosis, contain lipids in a phase separated from the aqueous system. This phase may be a liquid (oil) or a more structured liquid crystalline phase. Since it is important to know the physical state of lipid molecules in aqueous systems-biologic systems being aqueous systems -the long term objectives of this proposal are: (1) to continue study of phase equilibria and physical state of model systems of lipids both in the dry state and in water: (2) to examine the fine structure and physical characteristics of the phases found (solid, liquid crystals, liquid): and (3) to correlate these model systems with actual physiologic and pathologic phenomena, especially (a) bile and the formation of gallstones, (b) the nature of the lipid lesions of atherosclerosis, (c) the chemical composition and physical state of the lipids in feces, and (d) the structure and function of the microvillous membrane of the intestine.